Advances in multimodal treatment for stage IIIA-N2 non-small cell lung cancer.
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ABSTRACT: Background and aim
In Stage IIIA-N2 non-small cell lung cancer (NSCLC), the accuracy of combined positron-emission tomography/computed tomography imaging (PET-CT), together with mediastinal staging techniques, has led to a wide range of challenging clinical scenarios in terms of therapeutic management. Concurrent chemoradiotherapy followed by consolidation immunotherapy remains the standard of care. In patients with potentially-resectable disease, surgery plays an important role in multimodal therapy. The introduction of targeted therapies and immune-checkpoint inhibitors has revolutionized multimodal treatment. In the present article, we review current treatment options and future trends in stage IIIA-N2 NSCLC.Relevance for patients
This article provides insight into the current status of multimodal treatment for NSCLC to support decision-making in routine clinical practice.
SUBMITTER: Montemuino Muniz S
PROVIDER: S-EPMC8177852 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC5949436 | biostudies-literature
Project description:The eighth edition of the American Joint Committee on Cancer (AJCC) staging system for lung cancer was introduced in 2017 and included major revisions, especially of stage III. For the subgroup stage IIIA-N2 non-small-cell lung cancer (NSCLC), surgical resection remains controversial due to heterogeneous disease entity. The aim of this study was to evaluate the clinicopathologic features and prognostic factors of patients with completely resected stage IIIA-N2 NSCLC. We retrospectively evaluated 77 consecutive patients with pathologic stage IIIA-N2 NSCLC (AJCC eighth edition) who underwent surgical resection with curative intent in China Medical University Hospital between 2006 and 2014. Survival analysis was conducted, using the Kaplan-Meier method. Prognostic factors predicting overall survival (OS) and disease-free survival (DFS) were analyzed, using log-rank tests and multivariate Cox proportional hazards models. Of the 77 patients with pathologic stage IIIA-N2 NSCLC examined, 35 (45.5%) were diagnosed before surgery and 42 (54.5%) were diagnosed unexpectedly during surgery. The mean age of patients was 59 years, and the mean length of follow-up was 38.1 months. The overall one-, three-, and five-year OS rates were 91.9%, 61.3%, and 33.5%, respectively. Multivariate analysis showed that tumor size <3 cm (hazards ratio (HR): 0.373, p = 0.003) and video-assisted thoracoscopic surgery (VATS) approach (HR: 0.383, p = 0.014) were significant predictors for improved OS. For patients with surgically treated, pathologic stage IIIA-N2 NSCLC, tumor size <3 cm and the VATS approach seemed to be associated with better prognosis.
| S-EPMC7290400 | biostudies-literature
Project description:BackgroundThe role lobectomy plays in stage IIIA/N2 non-small cell lung cancer (NSCLC) is controversial for a long time. What's more, no previous study concentrates on whether sublobectomy can improve survival outcome for these patients, so we performed this population-based study to investigate whether stage IIIA/N2 NSCLC can benefit from these two surgery types and compare survival outcomes after lobectomy and sublobectomy.MethodsA total of 21,638 patients diagnosed with stage IIIA/N2 NSCLC between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database matched our selection criteria. The study cohort included patients who received no surgery (n = 15,951), sublobectomy (n = 628) and lobectomy (n = 5,059). Kaplan-Meier method, Cox regression analyses, and inverse probability of treatment weighting (IPTW)-adjusted Cox regression were used to illustrate the influence of sublobectomy and lobectomy on overall survival (OS) rates in the study cohort and compare these two surgery types.ResultsMultivariable Cox regression analysis showed sublobectomy [HR: 0.584 (95%CI: 0.531-0.644), P-value <0.001; IPTW-adjusted HR: 0.619 (95%CI: 0.605-0.633), P-value <0.001] and lobectomy [HR: 0.439 (95%CI: 0.420-0.459), P-value <0.001; IPTW-adjusted HR: 0.441 (95%CI: 0.431-0.451), P-value <0.001] were both related to better OS rates compared with no surgery, and lobectomy exhibited better survival than sublobectomy [HR: 0.751 (95%CI: 0.680-0.830), P-value <0.001; IPTW-adjusted HR: 0.713 (95%CI: 0.696-0.731), P-value <0.001]. Moreover, the results in subgroup analyses based on age, tumor size and radiotherapy and chemotherapy strategy in all study cohort were consistent.ConclusionStage IIIA/N2 NSCLC patients could benefit from sublobectomy or lobectomy, and lobectomy provided better OS rates than sublobectomy.
| S-EPMC8696201 | biostudies-literature
Project description:Defining the optimal neoadjuvant strategy in early-stage and locoregional (N2) oncogenic-driven lung cancer remains a major challenge for the scientific community. Whereas significant advances have been achieved with the use of personalized medicine and targeted therapies in advanced stages, we are still far from translating the same magnitude of benefits into an earlier-stage disease. Perioperative strategies with neoadjuvant and adjuvant tyrosine kinase inhibitors in patients with EGFR and ALK gene alterations have yielded mixed results and further biomarker-driven trials are needed to shed more light on the significance of inhibiting the oncogenic signaling addiction at earlier stages of the disease and the conceivable value of incorporating more potent targeted inhibitors in this setting. Meanwhile, the landscape of early-stage lung cancer management is progressing rapidly, and we anticipate the incorporation of novel immunotherapeutic agents on the basis of this promising preliminary activity as induction strategies. Whether the benefits observed in the overall population can be translated into specific subsets of oncogenic-driven tumors is still unknown, but it clearly reinforces the importance of incorporating-sooner rather than later-a biomarker-testing strategy into the routine work-up of early-stage non-small cell lung cancer (NSCLC). There are still many challenges to overcome such as the need to stablish standardized surrogate endpoints and to define the optimal duration of perioperative treatment, as well as how to expedite patient recruitment using enrichment strategies for biomarker stratified trials. Despite the difficulties, we are living in exciting times and coming up on a new window of opportunities for achieving the ultimate goal of curing early-stage lung cancer and improving long-term outcomes by eliminating the minimal residual disease and reducing the risk for metastatic recurrence.
| S-EPMC7867758 | biostudies-literature
Project description:Locally advanced non-small cell lung cancer accounts for one third of non-small cell lung cancer (NSCLC) at the time of initial diagnosis and presents with a wide range of clinical and pathological heterogeneity. To date, the combined multimodality approach involving both local and systemic control is the gold standard for these patients, since occult distant micrometastatic disease should always be suspected. With the rapid increase in treatment options, the need for an interdisciplinary discussion involving oncologists, surgeons, radiation oncologists and radiologists has become essential. Surgery should be recommended to patients with non-bulky, discrete, or single-level N2 involvement and be included in the multimodality treatment. Resectable stage IIIA patients have been the subject of a number of clinical trials and retrospective analysis, discussing the efficiency and survival benefits on patients treated with the available therapeutic approaches. However, most of them have some limitations due to their retrospective nature, lack of exact pretreatment staging, and the involvement of heterogeneous populations leading to the awareness that each patient should undergo a tailored therapy in light of the nature of his tumor, its extension and his performance status.
| S-EPMC7465235 | biostudies-literature
Project description:BackgroundThe National Comprehensive Cancer Network (NCCN) guidelines did not give an explicit comparison of the efficacy between surgery and radiotherapy in treating Stage-III N2 non-small cell lung cancer (NSCLC) patients, leaving a paucity for clinical reference. Through this study, we try to locate the optimum treatment strategy including surgical type for these patients.MethodsA systematic literature search was performed from PubMed, Cochrane Library, Embase, and Google Scholars. The endpoints were overall survival (OS), mean OS, and progression-free survival (PFS). The treatments comprised radiotherapy, lobectomy, and pneumonectomy. Network meta-analysis was carried out for calculating the odds ratio (OR) for binary variants. All the analyses implemented Stata 17.0 MP.ResultsEight clinical trials reporting 1756 patients met the inclusion criteria. Radiotherapy and surgery were equivalent in improving patients' OS (OR = 0.842, 95% confidence interval [CI]: [0.645, 1.099]). The mean OS of patients were similar in terms of radiotherapy, lobectomy, and pneumonectomy. Besides, radiotherapy and surgery had equivalent effects in improving PFS (OR = 0.896, 95% CI: [0.718, 1.117]).ConclusionsSince lobectomy and pneumonectomy following neoadjuvant treatments had equivalent efficacy in prolonging OS for patients with stage-IIIA N2 NSCLC compared with definitive radiotherapy, young patients with favorable performance status (0) should try surgery to pursue better prognosis while elderly patients with unfavorable PS or radiosensitive pathology types should accept definitive radiotherapy. More high-quality clinical trials are needed to support our findings.
| S-EPMC9280794 | biostudies-literature
Project description:BackgroundThis study aimed to determine whether adjuvant therapy improves survival in patients with stage IIIA-N2 non-small cell lung cancer (NSCLC) after neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery.MethodsWe retrospectively reviewed 467 consecutive patients with stage IIIA-N2 NSCLC who received neoadjuvant CCRT followed by surgery between 2004 and 2013. From these, we identified 398 eligible patients and their clinical outcomes were compared according to whether adjuvant therapy was provided.ResultsIn total, 296 patients (74%) received adjuvant therapy consisting of chemotherapy alone (n=71) radiotherapy alone (n=118) and both chemotherapy and radiotherapy (n=107). Adjuvant therapy was not given to remaining 102 patients. Patients who receiving adjuvant therapy were significantly younger (P=0.001), and predominantly male (P=0.014) compared to patients who did not receive adjuvant therapy. Regarding to the pathologic response, the adjuvant therapy group had a significantly poor pathologic response. However, the 5-year overall survival (OS) rate did not significantly differ between the groups (adjuvant therapy group, 52.9%; no adjuvant therapy group, 54.9%; P=0.369). After adjusting for age, sex, type of operation, cell type and yp stage, adjuvant therapy was significantly associated with better OS (hazard ratio =0.59; 95% CI, 0.38-0.92; P=0.019) and disease free survival (hazard ratio =0.62; 95% CI, 0.44-0.87; P=0.006).ConclusionsOur data indicate that adjuvant therapy is more often given to patients with poor pathologic findings. Adjuvant treatment after trimodal therapy is a significant predictor of survival after adjustment of clinical variables.
| S-EPMC7330356 | biostudies-literature
Project description:To evaluate the safety and efficacy of combining Endostar antiangiogenic therapy with neoadjuvant chemotherapy for the treatment of stage IIIA (N2) NSCLC, we conducted a randomized, controlled, open-label clinical study of 30 NSCLC patients. Patients were randomly assigned to the test or control groups, which received either two cycles of an NP neoadjuvant chemotherapy regimen combined with Endostar or the NP regimen alone, respectively, at a 2:1 ratio. Efficacy was assessed after 3 weeks, and surgical resection occurred within 4 weeks, in the 26 patients who successfully completed treatment. While total response rates (RR) and clinical benefit rates (CBR) did not differ between the experimental groups, total tumor regression rates (TRR) were higher in the test group than in the control group. Median DFS and OS also did not differ between the test and control groups. Clinical perioperative indicators, including intraoperative blood loss, number of dissected lymph node groups, duration of postoperative indwelling catheter use, and time to postoperative discharge, were comparable in the test and control groups. Finally, hematological and non-hematological toxicities and postoperative pathological indicators, including down-staging ratio, complete resection ratio, and metastatic lymph node ratio, also did not differ between the groups. Overall, combining Endostar with NP neoadjuvant chemotherapy increased therapeutic efficacy without increasing adverse effects in stage IIIA-N2 NSCLC patients. This study is registered with ClinicalTrials.gov (number NCT02497118).
| S-EPMC5308751 | biostudies-literature
Project description:BackgroundThe patient prognosis after complete resection for pathologic stage IIIA(N2) non-small cell lung cancer (NSCLC) remains a significant concern. The clinical relevance of the host immune response to NSCLC has yet to be established. We aimed to investigate the prognostic value of tumor-infiltrating lymphocytes (TILs) in a uniform cohort of patients with completely resected stage IIIA(N2) NSCLC.MethodsFrom 2005 to 2012, consecutive patients with pathologic stage IIIA(N2) NSCLC who underwent complete resection at our institution were reviewed. For each case, full-face hematoxylin and eosin-stained sections from surgical specimens were evaluated for the TIL density. A published, recommended TIL scoring scale was followed. The patients were stratified into the TIL- or TIL+ group based on pathologic evaluation.ResultsData from 320 patients were included in the analysis. Based on a median follow-up duration of 30.8 months, a higher density of TILs was associated with an improved postoperative survival time (P = 0.06). Subgroup analyses indicated that this positive effect was the greatest for patients with squamous cell carcinoma (SCC; P = 0.03). Among those with SCC, the TIL+ patients experienced a significantly increased 3-year distant metastasis-free survival (DMFS) compared to the TIL- patients (60.6% versus 42.7%, P = 0.02). Multivariate analyses of the 93 patients with SCC tumors confirmed that TIL+ was an independent prognostic factor for an increased DMFS (HR = 0.39, 95%CI 0.17-0.87, P = 0.02) and a prolonged overall survival (OS; HR = 0.47, 95%CI 0.22-1.00, P = 0.05).ConclusionsOur data suggest a potential role of TILs in predicting the survival of patients with completely resected stage IIIA(N2) NSCLC. The beneficial effects of TILs were more pronounced in the prediction of the DMFS and the OS in patients with SCC. This parameter should be considered for prospective inclusion in clinical trials.
| S-EPMC4872781 | biostudies-literature
Project description:Background The role of postoperative radiotherapy (PORT) in resected stage IIIa-N2 non-small cell lung cancer (NSCLC) patients who have received adjuvant chemotherapy remains controversial. This study aimed to explore the value of PORT and determine which patients could benefit from PORT. Methods Stage IIIa-N2 NSCLC patients treated with surgery and adjuvant chemotherapy were identified from the Surveillance, Epidemiology and End Results (SEER) databases from 2004 to 2015. Eligible patients were divided into the following two groups: PORT group and non-PORT group. Overall survival (OS) was estimated by the Kaplan-Meier (KM) method, and differences in survival were evaluated with log-rank test. Long-term cause-specific mortality consisted of lung cancer-related mortality and non-lung cancer-related mortality was investigated through competing risk analysis. Cox regression analysis was performed to identify variables that significantly affected OS. Results We identified 2,347 eligible patients, after propensity score matching (PSM), 877 pairs were selected. Overall, there was no significant difference in OS between two groups, but the patients who received PORT had a lower lung cancer-related mortality rate. Subgroup analysis showed that PORT was associated with a significantly better OS and lower lung cancer-related mortality rate in patients with T2, grade I–II and positive/resected lymph node ratio (LNR) ≥0.31. The non-lung cancer-related mortality of PORT group was higher in the patients with squamous cell carcinoma, although the difference was not significant. The independent prognostic factors for OS were age, sex, grade, histology, the American Joint Committee on Cancer (AJCC) T stage and LNR. Conclusions Our results revealed that PORT appears to be the optimal treatment strategy in patients with AJCC T2, grade I–II and LNR ≥0.31. PORT may not be recommended for patients with squamous cell carcinoma.
| S-EPMC9372214 | biostudies-literature